World Journal of Diabetes最新文献

{"title":"Comparative analysis of Nε-carboxymethyl-lysine and inflammatory markers in diabetic and non-diabetic coronary artery disease patients","authors":"D. Shrivastav, Desh Deepak Singh, Rashid Mir, Pratishtha Mehra, Vimal Mehta, P. Dabla","doi":"10.4239/wjd.v14.i12.1754","DOIUrl":"https://doi.org/10.4239/wjd.v14.i12.1754","url":null,"abstract":"BACKGROUND\u0000 Coronary artery disease (CAD) is a major cause of death worldwide, and India contributes to about one-fifth of total CAD deaths. The development of CAD has been linked to the accumulation of Nε-carboxymethyl-lysine (CML) in heart muscle, which correlates with fibrosis.\u0000 AIM\u0000 To assess the impact of CML and inflammatory markers on the biochemical and cardiovascular characteristics of CAD patients with and without diabetes.\u0000 METHODS\u0000 We enrolled 200 consecutive CAD patients who were undergoing coronary angiography and categorized them into two groups based on their serum glycosylated hemoglobin (HbA1c) levels (group I: HbA1c ≥ 6.5; group II: HbA1c < 6.5). We analyzed the levels of lipoproteins, plasma HbA1c levels, CML, interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and nitric oxide.\u0000 RESULTS\u0000 Group I (81 males and 19 females) patients had a mean age of 54.2 ± 10.2 years, with a mean diabetes duration of 4.9 ± 2.2 years. Group II (89 males and 11 females) patients had a mean age of 53.2 ± 10.3 years. Group I had more severe CAD, with a higher percentage of patients with single vessel disease and greater stenosis severity in the left anterior descending coronary artery compared to group II. Group I also exhibited a larger left atrium diameter. Group I patients exhibited significantly higher levels of CML, TNF-α, and IL-6 and lower levels of nitric oxide as compared with group II patients. Additionally, CML showed a significant positive correlation with IL-6 (r = 0.596, P = 0.001) and TNF-α (r = 0.337, P = 0.001) and a negative correlation with nitric oxide (r =-4.16, P = 0.001). Odds ratio analysis revealed that patients with CML in the third quartile (264.43-364.31 ng/mL) were significantly associated with diabetic CAD at unadjusted and adjusted levels with covariates.\u0000 CONCLUSION\u0000 CML and inflammatory markers may play a significant role in the development of CAD, particularly in diabetic individuals, and may serve as potential biomarkers for the prediction of CAD in both diabetic and non-diabetic patients.","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"7 21","pages":""},"PeriodicalIF":4.2,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139000247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Establishment of models to predict factors influencing periodontitis in patients with type 2 diabetes mellitus","authors":"Hong-Miao Xu, Xuan-Jiang Shen, Jia Liu","doi":"10.4239/wjd.v14.i12.1793","DOIUrl":"https://doi.org/10.4239/wjd.v14.i12.1793","url":null,"abstract":"BACKGROUND\u0000 Type 2 diabetes mellitus (T2DM) is associated with periodontitis. Currently, there are few studies proposing predictive models for periodontitis in patients with T2DM.\u0000 AIM\u0000 To determine the factors influencing periodontitis in patients with T2DM by constructing logistic regression and random forest models.\u0000 METHODS\u0000 In this a retrospective study, 300 patients with T2DM who were hospitalized at the First People’s Hospital of Wenling from January 2022 to June 2022 were selected for inclusion, and their data were collected from hospital records. We used logistic regression to analyze factors associated with periodontitis in patients with T2DM, and random forest and logistic regression prediction models were established. The prediction efficiency of the models was compared using the area under the receiver operating characteristic curve (AUC).\u0000 RESULTS\u0000 Of 300 patients with T2DM, 224 had periodontitis, with an incidence of 74.67%. Logistic regression analysis showed that age [odds ratio (OR) = 1.047, 95% confidence interval (CI): 1.017-1.078], teeth brushing frequency (OR = 4.303, 95%CI: 2.154-8.599), education level (OR = 0.528, 95%CI: 0.348-0.800), glycosylated hemoglobin (HbA1c) (OR = 2.545, 95%CI: 1.770-3.661), total cholesterol (TC) (OR = 2.872, 95%CI: 1.725-4.781), and triglyceride (TG) (OR = 3.306, 95%CI: 1.019-10.723) influenced the occurrence of periodontitis (P < 0.05). The random forest model showed that the most influential variable was HbA1c followed by age, TC, TG, education level, brushing frequency, and sex. Comparison of the prediction effects of the two models showed that in the training dataset, the AUC of the random forest model was higher than that of the logistic regression model (AUC = 1.000 vs AUC = 0.851; P < 0.05). In the validation dataset, there was no significant difference in AUC between the random forest and logistic regression models (AUC = 0.946 vs AUC = 0.915; P > 0.05).\u0000 CONCLUSION\u0000 Both random forest and logistic regression models have good predictive value and can accurately predict the risk of periodontitis in patients with T2DM.","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"326 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138996764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative study of type 2 diabetes mellitus-associated gut microbiota between the Dai and Han populations","authors":"Ling-Tong Tang, Lei Feng, Huiying Cao, Rui Shi, Bei-bei Luo, Yanbi Zhang, Yan-Mei Liu, Jian Zhang, Shuang-Yue Li","doi":"10.4239/wjd.v14.i12.1766","DOIUrl":"https://doi.org/10.4239/wjd.v14.i12.1766","url":null,"abstract":"BACKGROUND\u0000 The global prevalence of type 2 diabetes mellitus (T2DM) is increasing. T2DM is associated with alterations of the gut microbiota, which can be affected by age, illness, and genetics. Previous studies revealed that there are discriminating microbiota compositions between the Dai and the Han populations. However, the specific gut microbiota differences between the two populations have not been elucidated.\u0000 AIM\u0000 To compare the gut microbiota differences in subjects with and without T2DM in the Dai and Han populations.\u0000 METHODS\u0000 A total of 35 subjects of the Han population (including 15 healthy children, 8 adult healthy controls, and 12 adult T2DM patients) and 32 subjects of the Dai population (including 10 healthy children, 10 adult healthy controls, and 12 adult T2DM patients) were enrolled in this study. Fasting venous blood samples were collected from all the subjects for biochemical analysis. Fecal samples were collected from all the subjects for DNA extraction and 16S rRNA sequencing, which was followed by analyses of the gut microbiota composition.\u0000 RESULTS\u0000 No significant difference in alpha diversity was observed between healthy children and adults. The diversity of gut microbiota was decreased in T2DM patients compared to the healthy adults in both the Dai and Han populations. There was a significant difference in gut microbiota between healthy children and healthy adults in the Han population with an increased abundance of Bacteroidetes and decreased Firmicutes in children. However, this difference was less in the Dai population. Significant increases in Bacteroidetes in the Han population and Proteobacteria in the Dai population and decreases in Firmicutes in both the Han and Dai population were observed in T2DM patients compared to healthy adults. Linear discriminant analysis Effect Size analysis also showed that the gut microbiota was different between the Han and Dai populations in heathy children, adults, and T2DM patients. Four bacteria were consistently increased and two consistently decreased in the Han population compared to the Dai population.\u0000 CONCLUSION\u0000 Differences in gut microbiota were found between the Han and Dai populations. A significant increase in Bacteroidetes was related to the occurrence of T2DM in the Han population, while a significant increase in Proteobacteria was related to the occurrence of T2DM in the Dai population.","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"26 65","pages":""},"PeriodicalIF":4.2,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139000600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of the management and therapeutic performance of diabetes mellitus employing special target","authors":"Hong-Yan Sun, Xiao-Yan Lin","doi":"10.4239/wjd.v14.i12.1721","DOIUrl":"https://doi.org/10.4239/wjd.v14.i12.1721","url":null,"abstract":"Diabetes mellitus (DM) is a chronic metabolic condition characterized predominantly by hyperglycemia. The most common causes contributing to the pathophysiology of diabetes are insufficient insulin secretion, resistance to insulin’s tissue-acting effects, or a combination of both. Over the last 30 years, the global prevalence of diabetes increased from 4% to 6.4%. If no better treatment or cure is found, this amount might climb to 430 million in the coming years. The major factors of the disease’s deterioration include age, obesity, and a sedentary lifestyle. Finding new therapies to manage diabetes safely and effectively without jeopardizing patient compliance has always been essential. Among the medications available to manage DM on this journey are glucagon-like peptide-1 agonists, thiazolidinediones, sulphonyl urease, glinides, biguanides, and insulin-targeting receptors discovered more than 10 years ago. Despite the extensive preliminary studies, a few clinical observations suggest this process is still in its early stages. The present review focuses on targets that contribute to insulin regulation and may be employed as targets in treating diabetes since they may be more efficient and secure than current and traditional treatments.","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"5 34","pages":""},"PeriodicalIF":4.2,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139000969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential therapeutic targets for the prevention of diabetic nephropathy: Glycyrrhetinic acid","authors":"Lu Cai, Michael Horowitz, Md Shahidul Islam","doi":"10.4239/wjd.v14.i12.1717","DOIUrl":"https://doi.org/10.4239/wjd.v14.i12.1717","url":null,"abstract":"Uncontrolled hyperglycemia or poorly managed disease increases the propensity for a number of diabetes-related complications targeting major organs including the heart, eyes, and kidney. Although the mechanisms by which diabetes induces cardiovascular diseases include oxidative stress and inflammation, when insulin resistance remains the key to the pathogenesis, as implicated in the two reviews in this issue. This editorial mainly comments on the potential preventive application of glycyrrhetinic acid (or 18β-GA) in relation to diabetic nephropathy. The thera-peutic or preventive effects of 18β-GA, as a hydrolytic product of glycyrrhizic acid that is a component of licorice, have been appreciated in other disorders, but have received much less attention in relation to diabetic complications. A study in this issue has identified 18β-GA as a therapeutic for preventing diabetic nephropathy and provides evidence to support efficacy in cultured human renal tubule cells in vitro . Although it represents a pilot study, the observations support a new therapeutic approach that warrants further ex-ploration.","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"8 32","pages":""},"PeriodicalIF":4.2,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138999178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early hemodynamics after tibial transverse transport in patients with nonarterial stenosis and arterial stenosis diabetic foot","authors":"Mei-Mei Liao, Sen Chen, Jia-Rui Cao, Meng-Wei Wang, Zhi-hui Jin, Jia Ye, Yi-Jun Ren, Rui-Qiang Guo","doi":"10.4239/wjd.v14.i12.1784","DOIUrl":"https://doi.org/10.4239/wjd.v14.i12.1784","url":null,"abstract":"BACKGROUND\u0000 The diagnosis of peripheral arteriopathy in the diabetic foot is complicated by diabetes and its advanced complications. It has been found that diabetic foot can be categorized into arterial stenosis and non-arterial stenosis, both of which have significant differences in hemodynamic characteristics.\u0000 AIM\u0000 To evaluate the early hemodynamic changes in diabetic foot patients with nonarterial stenosis and arterial stenosis treated by tibial transverse transport (TTT) using high-frequency color Doppler ultrasonography (HFCDU) and a laser Doppler flowmeter.\u0000 METHODS\u0000 Twenty-five patients with Wagner grades 3-5 diabetic foot ulcers were treated with TTT, and the wound healing time and rate were recorded. Patients were grouped according to the results of preoperative lower-extremity ultrasonography. Cases with ≥ 50% stenosis in any of the femoral, popliteal, posterior tibial, anterior tibial, and peroneal arteries of the affected limb were classified as the arterial stenosis group (n = 16); otherwise, they were classified as the nonarterial stenosis group (n = 9). Before and one month after surgery, HFCDU was used to evaluate the degree of lower limb artery lesions and hemodynamic changes in patients. The degree of femoral-popliteal atherosclerotic stenosis, the degree of vascular stenosis and occlusion of the lower-knee outflow tract, and the degree of medial arterial calcification were scored; the three scores were added together to obtain the total score of lower extremity arteriopathy. PeriScanPIM3, a laser Doppler flowmeter system, was used to detect alterations in plantar microcirculation before and 1 mo after surgery. Wound healing and hemodynamic indices were compared between the two groups.\u0000 RESULTS\u0000 The wound healing time of the diabetic foot was significantly shorter in the nonarterial stenosis group than in the arterial stenosis group (47.8 ± 13 vs 85.8 ± 26, P &lt; 0.05), and the wound healing rate of both groups was 100%. The preoperative total lower extremity arteriopathy scores were lower in the nonarterial stenosis group than those in the arterial stenosis group (18.89 ± 8.87 vs 24.63 ± 3.52, P &lt; 0.05). The nonarterial stenosis group showed higher preoperative popliteal artery (POA) blood flow than the arterial stenosis group (204.89 ± 80.76 cc/min vs 76.75 ± 48.49 cc/min, P &lt; 0.05). Compared with the baseline (before surgery), the postoperative POA blood flow of the affected limb in the nonarterial stenosis group decreased one month after surgery (134.11 ± 47.84 cc/min vs 204.89 ± 80.76 cc/min, P &lt; 0.05), while that in the arterial stenosis group increased (98.44 ± 30.73 cc/min vs 61.69 ± 21.70 cc/min, P &lt; 0.05). Although the POA blood flow in the arterial stenosis group was obviously improved one month after surgery, it was still lower than that in the nonarterial stenosis group (98.44 ± 30.73 cc/min vs 134.11 ± 47.84 cc/min, P &lt; 0.05). The nonarterial stenosis group had higher preoperative plantar microcirculation than the a","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"149 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138997306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relationship between GCKR gene rs780094 polymorphism and type 2 diabetes with albuminuria","authors":"Yi-Ying Liu, Qin Wan","doi":"10.4239/wjd.v14.i12.1803","DOIUrl":"https://doi.org/10.4239/wjd.v14.i12.1803","url":null,"abstract":"BACKGROUND\u0000 Diabetic kidney disease is one of the common complications of type 2 diabetes (T2D). There are no typical symptoms in the early stage, and the disease will progress to moderate and late stage when albuminuria reaches a high level. Treatment is difficult and the prognosis is poor. At present, the pathogenesis of diabetic kidney disease is still unclear, and it is believed that it is associated with genetic and environmental factors.\u0000 AIM\u0000 To explore the relationship between the glucokinase regulatory protein (GCKR ) gene rs780094 polymorphism and T2D with albuminuria.\u0000 METHODS\u0000 We selected 252 patients (126 males and 126 females) with T2D admitted to our hospital from January 2020 to October 2020, and 66 healthy people (44 females and 22 males). According to the urinary albumin/creatinine ratio, the subjects were divided into group I (control), group II (T2D with normoalbuminuria), group III (T2D with microalbuminuria), and group IV (T2D with macroalbuminuria). Additionly, the subjects were divided into group M (normal group) or group N (albuminuria group) according to whether they developed albuminuria. We detected the GCKR gene rs780094 polymorphism (C/T) of all subjects, and measured the correlation between GCKR gene rs780094 polymorphism (C/T) and T2D with albuminuria.\u0000 RESULTS\u0000 Gene distribution and genotype distribution among groups I-IV accorded with the Hardy-Weinberg equilibrium. Genotype frequency was significantly different among the four groups (P = 0.048, χ 2 = 7.906). T allele frequency in groups II, III, and IV was significantly higher than that in group I. Logistic regression analysis of the risk factors for T2D with albuminuria showed that the CT + TT genotype (odds ratio = 1.710, 95% confidence interval: 1.172-2.493) was a risk factor.\u0000 CONCLUSION\u0000 CT + TT genotype is a risk factor for T2D with albuminuria. In the future, we can assess the risk of individuals carrying susceptible genes to delay the onset of T2D.","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"57 12","pages":""},"PeriodicalIF":4.2,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138999155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atorvastatin ameliorated myocardial fibrosis in db/db mice by inhibiting oxidative stress and modulating macrophage polarization","authors":"Xian-Min Song, Mengnan Zhao, Gui-Zhi Li, Na Li, Ting Wang, Hong Zhou","doi":"10.4239/wjd.v14.i12.1849","DOIUrl":"https://doi.org/10.4239/wjd.v14.i12.1849","url":null,"abstract":"BACKGROUND\u0000 People with diabetes mellitus (DM) suffer from multiple chronic complications due to sustained hyperglycemia, especially diabetic cardiomyopathy (DCM). Oxidative stress and inflammatory cells play crucial roles in the occurrence and progression of myocardial remodeling. Macrophages polarize to two distinct phenotypes: M1 and M2, and such plasticity in phenotypes provide macrophages various biological functions.\u0000 AIM\u0000 To investigate the effect of atorvastatin on cardiac function of DCM in db/db mice and its underlying mechanisms.\u0000 METHODS\u0000 DCM mouse models were established and randomly divided into DM, atorvastatin, and metformin groups. C57BL/6 mice were used as the control. Cardiac function was evaluated by echocardiography. Hematoxylin and eosin and Masson staining was used to examine the morphology and collagen fibers in myocardial tissues. The expression of transforming growth factor-β1 (TGF-β1), tumor necrosis factor-α (TNF-α), interleukin-1 β (IL-1β),M1 macrophages (iNOS+), and M2 macrophages (CD206+) were demonstrated by immunohistochemistry and immunofluorescence staining. The levels of TGF-β1, IL-1β, and TNF-α were detected by ELISA and real-time quantitative polymerase chain reaction. Malondialdehyde (MDA) concentrations and superoxide dismutase (SOD) ac-tivities were also measured.\u0000 RESULTS\u0000 Treatment with atorvastatin alleviated cardiac dysfunction and decreased db/db mice. The broken myocardial fibers and deposition of collagen in the myocardial interstitium were relieved especially by atorvastatin treatment. Atorvastatin also reduced the levels of serum lactate dehydrogenase, creatine kinase isoenzyme, and troponin; lowered the levels of TGF-β1, TNF-α and IL-1β in serum and myocardium; decreased the concentration of MDA and increased SOD activity in myocardium of db/db mice; inhibited M1 macrophages; and promoted M2 macrophages.\u0000 CONCLUSION\u0000 Administration of atorvastatin attenuates myocardial fibrosis in db/db mice, which may be associated with the antioxidative stress and anti-inflammatory effects of atorvastatin on diabetic myocardium through modulating macrophage polarization.","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"37 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139000112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diabetes mellitus and prostate cancer risk: A mendelian randomization analysis","authors":"Jian-Xu Yuan, Qing Jiang, Sheng-Jie Yu","doi":"10.4239/wjd.v14.i12.1839","DOIUrl":"https://doi.org/10.4239/wjd.v14.i12.1839","url":null,"abstract":"BACKGROUND\u0000 Some studies have directed towards an association between diabetes mellitus (DM) and prostate cancer (PCa); however, this specific relationship remains inconclusive. In recent years, Mendelian randomization (MR) has become a widely used analytical method for inferring epidemiological causes.\u0000 AIM\u0000 To investigated the potential relationship between DM and PCa using MR.\u0000 METHODS\u0000 We downloaded relevant data on \"diabetes\" and \"PCa\" from the IEU OpenGWAS project database, performed three different methods to conduct MR, and carried out sensitivity analysis for verification.\u0000 RESULTS\u0000 The results indicated that DM was an independent risk factor for PCa. The odds ratio (OR) values obtained using the inverse variance weighted method in this study were as follows: OR = 1.018 (95% confidence interval: 1.004-1.032), P = 0.014.\u0000 CONCLUSION\u0000 We found that DM could increase the incidence rate of PCa.","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"9 14","pages":""},"PeriodicalIF":4.2,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138970641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Empagliflozin ameliorates diabetic cardiomyopathy probably via activating AMPK/PGC-1α and inhibiting the RhoA/ROCK pathway","authors":"Na Li, Qiu-Xiao Zhu, Gui-Zhi Li, Ting Wang, Hong Zhou","doi":"10.4239/wjd.v14.i12.1862","DOIUrl":"https://doi.org/10.4239/wjd.v14.i12.1862","url":null,"abstract":"BACKGROUND\u0000 Diabetic cardiomyopathy (DCM) increases the risk of hospitalization for heart failure (HF) and mortality in patients with diabetes mellitus. However, no specific therapy to delay the progression of DCM has been identified. Mitochondrial dysfunction, oxidative stress, inflammation, and calcium handling imbalance play a crucial role in the pathological processes of DCM, ultimately leading to cardiomyocyte apoptosis and cardiac dysfunctions. Empagliflozin, a novel glucose-lowering agent, has been confirmed to reduce the risk of hospitalization for HF in diabetic patients. Nevertheless, the molecular mechanisms by which this agent provides cardioprotection remain unclear.\u0000 AIM\u0000 To investigate the effects of empagliflozin on high glucose (HG)-induced oxidative stress and cardiomyocyte apoptosis and the underlying molecular mechanism.\u0000 METHODS\u0000 Twelve-week-old db/db mice and primary cardiomyocytes from neonatal rats stimulated with HG (30 mmol/L) were separately employed as in vivo and in vitro models. Echocardiography was used to evaluate cardiac function. Flow cytometry and TdT-mediated dUTP-biotin nick end labeling staining were used to assess apoptosis in myocardial cells. Mitochondrial function was assessed by cellular ATP levels and changes in mitochondrial membrane potential. Furthermore, intracellular reactive oxygen species production and superoxide dismutase activity were analyzed. Real-time quantitative PCR was used to analyze Bax and Bcl-2 mRNA expression. Western blot analysis was used to measure the phosphorylation of AMP-activated protein kinase (AMPK) and myosin phosphatase target subunit 1 (MYPT1), as well as the peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and active caspase-3 protein levels.\u0000 RESULTS\u0000 In the in vivo experiment, db/db mice developed DCM. However, the treatment of db/db mice with empagliflozin (10 mg/kg/d) for 8 wk substantially enhanced cardiac function and significantly reduced myocardial apoptosis, accompanied by an increase in the phosphorylation of AMPK and PGC-1α protein levels, as well as a decrease in the phosphorylation of MYPT1 in the heart. In the in vitro experiment, the findings indicate that treatment of cardiomyocytes with empagliflozin (10 μM) or fasudil (FA) (a ROCK inhibitor, 100 μM) or overexpression of PGC-1α significantly attenuated HG-induced mitochondrial injury, oxidative stress, and cardiomyocyte apoptosis. However, the above effects were partly reversed by the addition of compound C (CC). In cells exposed to HG, empagliflozin treatment increased the protein levels of p-AMPK and PGC-1α protein while decreasing phosphorylated MYPT1 levels, and these changes were mitigated by the addition of CC. Adding FA and overexpressing PGC-1α in cells exposed to HG substantially increased PGC-1α protein levels. In addition, no sodium-glucose cotransporter (SGLT)2 protein expression was detected in cardiomyocytes.\u0000 CONCLUSION\u0000 Empagliflozin partially achieves anti-oxidative","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"115 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138999532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}